Plasma Steroid Trajectories From Day‐of‐Surgery Baseline After Robot‐Assisted Radical Prostatectomy for Prostate Cancer

BACKGROUND: Circulating steroid trajectories after robot-assisted radical prostatectomy are poorly characterized from the day-of-surgery baseline, and relevant biology extends beyond testosterone and dihydrotestosterone to adrenal-derived 11-oxygenated androgens and steroid conjugate turnover. This study aimed to characterize 3- and 6-month plasma steroid differences from a day-of-surgery baseline and evaluate baseline steroid biomarkers for adverse pathology, upgrading, and early detectable prostate-specific antigen (PSA). METHODS: This prospective, single-center cohort included 173 men undergoing robot-assisted radical prostatectomy. Fasting plasma was sampled before premedication on the morning of surgery and at 3 and 6 months. A 34-analyte steroid panel, including conjugated analytes, was quantified using liquid chromatography-tandem mass spectrometry. Longitudinal differences were analyzed using mixed-effects models. Baseline screening used logistic regression with false discovery rate correction and adjusted models for retained signals. RESULTS: For most analytes, 168-170 baseline samples and 131/108 samples at 3/6 months were available. Relative to baseline, 11-ketotestosterone increased at 3 and 6 months (fold changes 1.36 [95% CI 1.24-1.49] and 1.25 [1.13-1.38]), corticosterone decreased (0.61 [0.52-0.70] and 0.59 [0.51-0.69]), cortisol decreased (0.91 [0.84-1.00] and 0.86 [0.78-0.94]), and conjugated corticosterone/corticosterone increased (1.96 [1.57-2.45] and 2.41 [1.90-3.06]), all p < 0.04. At 6 months, neither testosterone (fold change 0.88; 95% CI 0.75-1.03) nor dihydrotestosterone (0.90; 0.79-1.04) differed significantly from the day-of-surgery baseline. The conjugated/unconjugated estrone ratio (E1C/E1) was the only retained baseline adverse-pathology signal, with inverse adjusted associations for pT3a/b disease (OR 0.61; 95% CI 0.41-0.90; p = 0.013) and composite adverse pathology (OR 0.53; 95% CI 0.36-0.78; p = 0.001). No biomarker remained significant for upgrading or detectable PSA. CONCLUSIONS: Relative to the day-of-surgery baseline, longitudinal differences involve corticosteroid-related and 11-oxygenated analytes, but their mechanisms remain unresolved. These data define postoperative steroid trajectories from a day-of-surgery baseline without establishing prostatectomy-specific endocrine effects. Baseline E1C/E1 warrants external validation as a hypothesis-generating marker of adverse pathology.